A case study of a pulmonary fibrosis patient who was ultimately diagnosed with liver cirrhosis and a telomere length disorder, highlighted the need to consider whether short telomere syndrome is present in people with lung fibrosis and cirrhotic liver.
The man in the case report was a 43-year-old heavy smoker with labored breathing upon exertion and an enlarged liver. The physicians noted that the man had severely impaired gas exchange with only a low-level of lung obstruction, suggesting that interstitial lung disease was present. This was supported by a chest computed tomography (CT) scan. A lung biopsy further showed subpleural interstitial fibrosis, mild superimposed acute lung injury, and focal bronchiectasis. Based on all the features observed, the man received an idiopathic pulmonary fibrosis (IPF) diagnosis.
The chest CT had indicated that the patient had liver cirrhosis. But further investigation showed that signs or risk factors for chronic liver disease, such as heavy alcohol consumption or metabolic syndrome, were not present, and infectious, or autoimmune components, could not be detected. Cirrhosis was later confirmed by a liver biopsy. The patient also had an abnormally high blood pressure in the main vein leaving the liver.
The combined findings made the clinicians suspect a telomere disorder. Telomeres are repetitive DNA sequences capping the ends of a chromosome. Their function is to protect the chromosome from wearing down or fusing with other chromosomes. The telomeres become shorter with time but are renewed by telomerase enzymes.
Telomere shortening can be the result of both genetic or environmental factors, and shortened telomere length increases the risk of fibrosis and, eventually, of multi-organ failure. Other studies have shown that IPF is indeed the most common sign of telomere shortening.
Genetic testing showed that the man did not have any mutations in the genes TERT and TERC, commonly affected in telomere shortening, but an analysis of the patient’s telomeres revealed that they were substantially shorter than could be expected given his age. Based on the findings, the clinicians concluded that the man likely had an unknown mutation in his telomerase genes.
The authors said the findings highlighted the need to consider telomere shortening syndrome in the differential diagnosis of patients with cryptogenic cirrhosis, especially if they have other manifestations of organ fibrosis.